She was born Edith Goodall on September 2, 1896 in Louisville, Kentucky. Her first professional experience came in 1919 in Louisville's Park Theater. The singer Lena Wilson and her brother, Danny, performed in Louisville; Edith married Danny and joined their act. Danny, a pianist who had been trained at a conservatory in Charleston, South Carolina, encouraged Lena and Edith to sing not just blues but also other song forms. Together the trio performed on the East Coast in 1920–1921, and when they were in New York City Wilson was signed by Columbia, which recorded her in 1921 with Johnny Dunn's Jazz Hounds. She recorded 17 songs with Dunn in 1921 and 1922. In 1924 she worked with Fletcher Henderson in New York, where she was slated to sing with Coleman Hawkins, but Hawkins refused to perform because he wanted additional compensation. She remained a popular Columbia artist through 1925.
Wilson recorded far less than other female blues stars of the 1920s like Bessie Smith. After Wilson left Columbia in 1925, she recorded one record for Brunswick in 1929 and a handful of sides for Victor in 1930. She remained a nightclub and theater singer, working for years on the New York entertainment scene. She sang with Florence Mills in the Lew Leslie Plantation Review in Harlem. She also made several trips to England, where she was well received. She sang with The Hot Chocolates revue, performing alongside Louis Armstrong and Fats Waller, and made appearances with Bill Robinson, Duke Ellington, Alberta Hunter, Cab Calloway, and Noble Sissle.
Wilson also did extensive work as an actress, appearing on radio in Amos and Andy and on film in To Have and Have Not (1944). Shortly after World War II she became the face of Aunt Jemima pancake mix. She retired from active performance in 1963, becoming executive secretary for the Negro Actors Guild, but made a comeback in 1973 to play with Eubie Blake, Little Brother Montgomery, and Terry Waldo. Her last live show was at the 1980 Newport Jazz Festival.